Administration	Common drugs and dosing	Onset of action (minutes)	Stage of labor	Challenges/limitations	Evidence
Parenteral opioids12–17
Patient-controlled intravenous, intravenous bolus, or intramuscular	Butorphanol, 1 to 2 mg IM or IV every 4 to 6 hours	5 to 10 (IV), 30 to 60 (IM)	First	Evidence for pain control only within first two hours of administration; common maternal adverse effects: nausea, vomiting, dizziness, respiratory depression, oxygen desaturation, sedation; decreased fetal heart rate variability; crosses placenta, increased risk of neonatal respiratory depression when administered close to delivery; butorphanol and nalbuphine can precipitate withdrawal in patients taking chronic opioids	Better pain control than parenteral nonopioid medications and nitrous oxide but inferior to neuraxial anesthesia
	Fentanyl, 25 to 50 mcg IV every hour	2 to 4 (IV)
	Morphine, 2 to 4 mg IM or IV every 2 to 4 hours (5 to 10 mg IM may be used in latent labor)	3 (IV), 40 (IM)
	Nalbuphine, 10 to 20 mg IM, IV, or SQ every 3 hours	2 to 3 (IV), 15 (IM or SQ)
	Remifentanil (Ultiva), typically used as a background infusion of 0.05 to 0.1 mcg per kg plus boluses of 0.2 to 0.5 mcg per kg with lockout intervals of 2 to 3 minutes	1 to 2
Parenteral nonopioids (analgesics, antihistamines, sedatives)16,18–21
Oral, intravenous, or intramuscular	Acetaminophen, 1,000 mg orally or IV every 6 hours	60 (IV), 10 (oral)	First	Acetaminophen: may not control pain adequately	Improves pain scores but less than parenteral opioids
	Diphenhydramine (Benadryl), 25 to 50 mg orally, IV, or IM every 4 to 6 hours	1 (IV), 5 (IM)		Diphenhydramine and promethazine: maternal somnolence and dissociation from birth
	Promethazine, 50 mg orally or IM or 25 mg IV every 4 to 6 hours	20 (oral and IM), 2 to 5 (IV)
Inhaled medication (nitrous oxide, fluranes)22,23
Self-administered via handheld mask	50:50 mix of nitrous oxide and oxygen gas	< 1	First and second	Maternal nausea, vomiting, dizziness, drowsiness; effect ends quickly once mask is removed; potent greenhouse gas	Improves pain scores; rapid clearance once mask is removed